Drug & supplement interaction

Grape + Acetaminophen, Phenylephrine, Chlorpheniramine

Acetaminophen, Phenylephrine, Chlorpheniramine brand name: Super Cold Tabs.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Phenylephrine, Chlorpheniramine falls into 3 drug categories that Grape can interact with; the most serious is rated moderate. Theoretically, grape juice might reduce the levels of CYP1A2 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grape and Acetaminophen, Phenylephrine, Chlorpheniramine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Grape interacts with whole categories of medication. Acetaminophen, Phenylephrine, Chlorpheniramine falls into 3 of those categories, so it can interact with Grape in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Acetaminophen, Phenylephrine, Chlorpheniramine

Acetaminophen, Phenylephrine, Chlorpheniramine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Grape interacts with.

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.
Severity Moderate Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for your Super Cold Tabs (which combines acetaminophen, phenylephrine, and chlorpheniramine). Grape juice may gently speed up an enzyme called CYP1A2, and in theory that could clear certain medicines a little faster. None of these three ingredients are prodrugs, so faster clearance would mean a slightly weaker effect, not a stronger one.

Honestly, though, this is pretty weak and theoretical evidence based on a small study using a different drug. For a short-term cold combo like this, drinking some grape juice or eating grapes is very unlikely to cause a real problem. If you take concentrated grape seed extract regularly, it's worth a quick chat with your pharmacist to be safe.

References
  1. Xiao Dong S, Zhi Ping Z, Zhong Xiao W, et al. Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 1999;48:638-40. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Acetaminophen, Phenylephrine, Chlorpheniramine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the honest picture with grape seed extract and this cold-and-allergy combo (the acetaminophen, phenylephrine, and chlorpheniramine in Super Cold Tabs). Grape seed extract may nudge a liver enzyme called CYP3A4, which helps process some of these ingredients. The catch is that the research can't agree on the direction. Lab studies hint it might slow the enzyme, while animal studies suggest it might speed it up. None of this is a prodrug situation, so there's no flip to worry about.

Practically, this hasn't actually shown up as a problem in people, and the evidence is only test-tube and animal level. Food amounts of grapes are a non-issue. If you're taking a concentrated grape seed supplement, just mention it to your pharmacist or doctor before combining.

References
  1. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  2. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 3

Acetaminophen, Phenylephrine, Chlorpheniramine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the piece that matters with this combo cold tablet: the acetaminophen part is partly handled by a liver enzyme called CYP2E1. Lab and animal studies hint that concentrated grape seed extract might slow that enzyme down. In theory, that could let a bit more acetaminophen hang around. But honestly, this has never actually been seen in people, so I wouldn't lose sleep over it.

A couple of practical notes. Eating grapes or drinking grape juice almost certainly won't do anything here, this is really only a question with strong supplement doses. And the bigger acetaminophen rule still stands: watch your total daily dose and go easy on alcohol. If you take a grape supplement regularly, just give your pharmacist a heads-up.

References
  1. Ray, S. D., Parikh, H., Hickey, E., Bagchi, M., and Bagchi, D. Differential effects of IH636 grape seed proanthocyanidin extract and a DNA repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent aniline hydroxylation. Mol Cell B PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Grape Also Interacts With Other Medications

Grape has 867 moderate, 42 minor known drug interactions in our database — the Acetaminophen, Phenylephrine, Chlorpheniramine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Grape

Covers the 2,830 medications we’ve checked against Grape. Pick one to open its full report.

From our Q&A

Questions About Grape or Acetaminophen, Phenylephrine, Chlorpheniramine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grape or Acetaminophen, Phenylephrine, Chlorpheniramine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Phenylephrine, Chlorpheniramine

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Phenylephrine, Chlorpheniramine page lists 289 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Ephedra (major) and Grapefruit (major).

By severity: 14 major · 229 moderate · 46 minor.

From our pharmacist’s overview on the Acetaminophen, Phenylephrine, Chlorpheniramine page

“Super Cold Tabs earns more caution than a cold remedy usually gets. It combines acetaminophen, the decongestant phenylephrine, and the antihistamine chlorpheniramine, and 14 of the 289 supplements on file interact at a major level, so those are the ones to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Phenylephrine, Chlorpheniramine interaction page

One more smart check

Taking Grape as Part of a Dietary Supplement Product? Check It for Interactions

We hold 8,053 real supplement products containing Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grape. Your product may carry other ingredients that interact with Acetaminophen, Phenylephrine, Chlorpheniramine too, on top of Grape — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Grape and Acetaminophen, Phenylephrine, Chlorpheniramine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Grape
Top 5%

#33 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Phenylephrine, Chlorpheniramine
Top 10%

#280 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Grape

What is Grape?

Grape
  • Antioxidant support
  • Heart and circulation health
  • Vein problems (such as varicose veins)
  • Eye health
  • General anti-inflammatory support

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is healthy and generally safe, the supplement evidence for treating specific conditions is mostly limited or preliminary. Talk with your pharmacist or doctor before starting a grape supplement.

Read the full Grape monograph & all interactions
Keep checking

Other Drugs & Grape

Browse every other medication we’ve checked against Grape — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
867Moderate
42Minor
1,920No known interaction
Moderate

867 interactions

Showing 60 of 867 moderate interactions — see all 867 on the Grape page.

Minor

42 interactions

No interaction 1,920 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Grape and Acetaminophen, Phenylephrine, Chlorpheniramine Together: Common Questions

Can you take Grape with Acetaminophen, Phenylephrine, Chlorpheniramine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Grape and Acetaminophen, Phenylephrine, Chlorpheniramine?
Acetaminophen, Phenylephrine, Chlorpheniramine belongs to more than one drug category, and Grape interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Grape and Acetaminophen, Phenylephrine, Chlorpheniramine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.